Thread by @ChillaPharmD

“#Tramadont”, a #tweetorial

In response to the last #pharmacyeducationboard about tramadol- some are still doubting whether it has earned the moniker “Tramadont”. Points have been made that as tramadol is metabolized by CYP2D6 in the liver, so are other drugs. Should we (1/11)

just not prescribe anyone anything metabolized in the liver? Touché. The problem with CYP2D6 specifically is that it happens to have the most polymorphisms of all the CYPs enzymes. What does this mean? It means it has the greatest potential variability in activity (2/11)

from one person to another. Not only this, but unlike the other CYPs, it’s expression can vary from being absolutely nonfunctional to being an ultrarapid metabolizer because of the very unique ability of it to be duplicated! No other CYP enzyme does this!! (3/11)

So CYP2D6 is already unpredictable, but then you throw in this drug, tramadol, which has serotonergic and weak opioid activity from the parent compound and stronger opioid activity with the M1 metabolite (product of CYP2D6), (4/11)

now you have this crazy unpredictable wishywashy mishmash of serotonin and opioid effects! 🤪🤯 What about other opiates? Well yes, CYP2D6 metabolizes very many other opiates too, so you should always “start low and go slow” as they say. (5/11)

Some are metabolized more by CYP2D6 than others and some are metabolized by 5+ CYP enzymes, so a polymorphism in CYP2D6 isn’t going to be as impactful there as one in another opioid that has greater metabolism by CYP2D6. (6/11)

The whole problem with tramadol is that if you have a pt w a polymorphism of CYP2D6 that confers no activity, you basically get a SNRI (it inhibits NE reuptake too) and see much more than its usual serotonergic effects. (7/11)

If you have a ultrarapid metabolizer with duplicate copies of the gene, then you essentially overdose your patient on opiates. (8/11)

And, if perchance you end up with the Goldilocks tramadol patient who has just the right amount of CYP2D6 activity, then you end up with a lovely amount of analgesia with a sprinkling of happiness in there. (9/11)

But, there’s hope- it doesn’t have to be #tramadont, if you have a patient who you feel would be a could candidate for tramadol, go get their pharmacogenomic profile tested and find out, they could very well be the tramadol Goldilocks, in which case it could be helpful (10/11)

(as long as they don’t have any significant drug/disease interactions).
PMID 20828952, 24340040, 22288606
#twitterx #medtwitter #nursetwitter
Thank you all for the stimulating discussion! It’s my favorite part of Twitter. (11/11)